Variant rs28729117 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020919.4(ALS2):c.1114-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,504,302 control chromosomes in the GnomAD database, including 23,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2498 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20770 hom. )

Consequence

ALS2
NM_020919.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

ALS2 (HGNC:443): (alsin Rho guanine nucleotide exchange factor ALS2) The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ALS2 links:

ALS2 (HGNC:):

ALS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-201757786-T-C is Benign according to our data. Variant chr2-201757786-T-C is described in ClinVar as [Benign]. Clinvar id is 261365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALS2	NM_020919.4 linkuse as main transcript	c.1114-27A>G		intron_variant		ENST00000264276.11	NP_065970.2	Q96Q42-1A8K4R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALS2	ENST00000264276.11 linkuse as main transcript	c.1114-27A>G		intron_variant		1	NM_020919.4	ENSP00000264276.6		Q96Q42-1

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25719

AN:

151986

Hom.:

2498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.161

GnomAD3 exomes

AF:

0.218

AC:

43400

AN:

199222

Hom.:

5445

AF XY:

0.223

AC XY:

24582

AN XY:

110002

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.450

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.160

AC:

216950

AN:

1352198

Hom.:

20770

Cov.:

AF XY:

0.165

AC XY:

111931

AN XY:

676454

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.324

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.169

AC:

25737

AN:

152104

Hom.:

2498

Cov.:

AF XY:

0.175

AC XY:

13027

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.405

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.161

Alfa

AF:

0.151

Hom.:

343

Bravo

AF:

0.163

Asia WGS

AF:

0.370

AC:

1284

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.086

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over